The fundus of the human eye is the interior surface of the eye, opposite the lens, and includes the retina, optic disc, retinal pigment epithelium (RPE), and the choroid. The retina is a thin layer of neural tissue at the back of the eye that transforms light into electrical signals for the brain, and the choroid is a vascular layer of the eye under the retina. The retina can be divided into two distinct regions related to their visual function. These regions are the macula, where the majority of photoreceptor cells (responsible for central, high acuity color vision) lie, and the periphery, which includes everything outside the macula. The macula includes a region known as the fovea, which is responsible for our high acuity vision.
To observe and monitor the structure of the retina or choroid, physicians currently rely on various medical imaging techniques, such as fluorescein angiography (FA) imaging, indocyanine green (ICG) imaging, and fundus autofluorescence (FAF). FA/ICG allows physicians to observe the accumulation of fluid from retinal or choroidal vessels, the formation of new retinal or choroidal blood vessels, and the loss of perfusion of blood in retinal vessels and choroidal vessels which cause vision loss and retinal dysfunction. The leakage of fluid can be observed as a growing region of hyperfluoresence in time elapsed FA images in areas of the retina or beneath the retina where fluid leaks, formation of new blood vessels will be seen as hyperfluorescent networks of vessels and loss of perfusing blood vessels will be seen as areas of hypofluorescence in FA and ICG imaging.
FAF imaging relies on the inherent fluorescence of proteins and other molecules produced in the retina and RPE. The reflected light from these molecules is captured and transformed into an electrical signal (e.g., an electrical current) to be processed and displayed as a grayscale image of the retina. In such an image, areas exhibiting excessive accumulation of metabolic products (e.g., lipofuscin) appear bright as compared with surrounding tissue, and areas with decreased accumulation appear dark. Further, areas where cells have died completely (e.g., due to a process known as atrophy) appear black. Bright regions can be described as hyperfluorescent, and dark regions can be described as hypofluorescent. Both hyperfluorescent and hypofluorescent regions are disease signatures, or disease markers, that reflect dysfunction in retinal tissue, such as the photoreceptor cells described above.
Current FAF, FA, and ICG techniques rely on a subjective interpretation of disease signatures. Yet, hyperfluorescence and hypofluorescence are sometimes hard to visually distinguish from shadows or changes in FAF, FA, or ICG image acquisition gain and contrast, making subtle changes in disease signatures hard to quantify. As a result, FAF, FA, and ICG assessment has developed into a primarily descriptive, rather than quantifiable, process. Without an objective quantification process, variability in clinical grading can be a barrier to measuring the effectiveness of disease interventions or determining a prognosis to guide treatment.